Infant jaundice, or hyperbilirubinemia, is a significant clinical problem, occurring in about 5% of full-term infants. The syndrome is the direct result of increased bilirubin levels in the infant body. Adults also have problems with jaundice, but they are generally not as serious or as widespread because most adults are capable of conjugating excess bilirubin with sugars and clearing this toxin from the body. This detoxification mechanism is not fully developed in neonates. Nevertheless, some adults, such as those who have hepatitis or obstructions to bile flow, are subject to jaundice as well.
Various treatments have been suggested for both infant and adult jaundice when these problems occur. These treatments include phototherapy, exchange transfusions, extracorporeal filtration systems, and drugs which induce an efficient clearance system. None of these treatments is simple to administer or effective without negative side reactions, including risk of injury or death. If the jaundice is not promptly treated, serious damage to the nervous system can result, especially in infants, as the elevated amounts of bilirubin act as a neurotoxin, and the blood/brain barrier in infants is incompletely developed. Also, the foregoing treatments are administered after the fact--i.e., after the jaundice has already appeared.
In neonates, the visible signs of the disorder manifest themselves usually at about 72 hours after birth, often after the infant has left the hospital or birth center. Thus, the signs may appear when the baby is no longer under the observation of trained medical personnel. In order to minimize the organic and neurological damage caused by the elevated bilirubin levels, therefore, it is advantageous to intervene before control over treatment has been lost, which is often before the signs actually appear.
One aspect of effective intervention is the identification of individuals at risk for developing this syndrome. Because, in order to eliminate as totally as possible the incidence of neonatal jaundice, every infant must be tested, effective prediction requires a simple, noninvasive procedure. Measurement of bilirubin in the blood per se is not a satisfactory approach because accurate prediction of a potential to develop jaundice rests on detection of increased bilirubin production, as opposed to the levels of bilirubin in the blood. Blood bilirubin levels are influenced not only by production, of course, but also by rates of excretion, and hepatic and intestinal uptake.
The parent application herein discloses and claims a protocol for effective prevention of the occurrence of neonatal jaundice in an infant population. The disclosure of this application, now issued as U.S. Pat. No. 4,831,024 is incorporated herein by reference. The disclosed method involves testing each member of the infant population for high levels of carbon monoxide exhalation, and treating those members of the population perceived to be at risk with a zinc porphyrin derivative, preferably zinc mesoporphyrin or zinc protoporphyrin. Only generalized directions for the formulation of the zinc porphyrin drug are disclosed.
In addition to the use of zinc porphyrin derivatives in the treatment of jaundice, both in neonates and in adults, other groups have suggested the use of alternative metalloporphyrins, including tin, chromium and manganese porphyrin derivatives. While it is believed that the overall result from the use of zinc analogs is most desirable, other workers may prefer to use these other metallo derivatives.
In all cases, formulation has been difficult because of the insolubility of the relevant metalloporphyrin in water, even in the presence of mineral base. Administration of any of these compounds is greatly enhanced by a formulation which permits suitably high concentrations to be achieved.